{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:20:05Z","timestamp":1792686005684,"version":"4.5.0"},"reference-count":89,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":48,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01AI150181,R01AI136529,R21AI152499,K08AI14755,R01AI132638,R01AI176658,R01GM092804"],"award-info":[{"award-number":["R01AI150181,R01AI136529,R21AI152499,K08AI14755,R01AI132638,R01AI176658,R01GM092804"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005294","name":"Massachusetts General Hospital","doi-asserted-by":"crossref","award":["Fund for Medical Discovery Research Fellowship"],"award-info":[{"award-number":["Fund for Medical Discovery Research Fellowship"]}],"id":[{"id":"10.13039\/100005294","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,24]]},"abstract":"<jats:p>\n                    Inhibition of Bruton\u2019s tyrosine kinase (BTK) through covalent modifications of its active site (e.g.\n                    <jats:italic>,<\/jats:italic>\n                    ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies. However, IBT-treated patients are more susceptible to invasive fungal infections, although the mechanism is poorly understood. Neutrophils are the primary line of defense against these infections; therefore, we examined the effect of IBT on primary human neutrophil effector activity against\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    . IBT significantly impaired the ability of neutrophils to kill\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    and potently inhibited reactive oxygen species (ROS) production, chemotaxis, and phagocytosis. Importantly, exogenous TNF-\u03b1 fully compensated for defects imposed by IBT and newer-generation BTK inhibitors and restored the ability of neutrophils to contain\n                    <jats:italic>A<\/jats:italic>\n                    .\n                    <jats:italic>fumigatus<\/jats:italic>\n                    hyphal growth. Blocking TNF-\u03b1 did not affect ROS production in healthy neutrophils but prevented exogenous TNF-\u03b1 from rescuing the phenotype of IBT-treated neutrophils. The restorative capacity of TNF-\u03b1 was independent of transcription. Moreover, the addition of TNF-\u03b1 immediately rescued ROS production in IBT-treated neutrophils, indicating that TNF-\u03b1 worked through a BTK-independent signaling pathway. Finally, TNF-\u03b1 restored effector activity of primary neutrophils from patients on IBT therapy. Altogether, our data indicate that TNF-\u03b1 rescued the antifungal immunity block imposed by inhibition of BTK in primary human neutrophils.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.176162","type":"journal-article","created":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T14:00:36Z","timestamp":1719151236000},"source":"Crossref","is-referenced-by-count":16,"title":["BTK inhibitor\u2013induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-\u03b1"],"prefix":"10.1172","volume":"9","author":[{"given":"Diego A.","family":"Vargas-Blanco","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA."},{"name":"Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia W.","family":"Hepworth","sequence":"additional","affiliation":[{"name":"Division of 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